Altered expression of angiogenesis-related placental genes in pre-eclampsia associated with intrauterine growth restriction

Järvenpää, Jouko; Vuoristo, Jussi; Savolainen, Eeva‐Riitta; Ukkola, Olavi; Vaskivuo, Tommi; Ryynänen, Markku

doi:10.1080/09513590701350291

Cited by 57 publications

(32 citation statements)

References 25 publications

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“…As an illustration, EPAS1 or CALB3 were found to be up-regulated in the IC and the C areas of SCNT recipient cows respectively. EPAS1 (also known as HIF-2 ␣) is a transcription factor participating to the cellular response to hypoxia, stabilizing the vascular maturation in human angiogenesis (19) and increased with preeclampsia in women endometrium (20). The role of EPAS1 in the bovine placentation is not yet established but EPAS1 up-regulation in SCNT pregnancies is in keeping with the increase of HIF-1␣ recently reported in bovine SCNT pregnancies at day 30 (21).…”

Section: Discussionmentioning

confidence: 52%

Endometrium as an early sensor of in vitro embryo manipulation technologies

Mansouri-Attia

Sandra

Aubert

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

199

185

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Implantation is crucial for placental development that will subsequently impact fetal growth and pregnancy success with consequences on postnatal health. We postulated that the pattern of genes expressed by the endometrium when the embryo becomes attached to the mother uterus could account for the final outcome of a pregnancy. As a model, we used the bovine species where the embryo becomes progressively and permanently attached to the endometrium from day 20 of gestation onwards. At that stage, we compared the endometrial genes profiles in the presence of an in vivo fertilized embryo (AI) with the endometrial patterns obtained in the presence of nuclear transfer (SCNT) or in vitro fertilized embryos (IVF), both displaying lower and different potentials for term development. Our data provide evidence that the endometrium can be considered as a biological sensor able to fine-tune its physiology in response to the presence of embryos whose development will become altered much later after the implantation process. Compared with AI, numerous biological functions and several canonical pathways with a major impact on metabolism and immune function were found to be significantly altered in the endometrium of SCNT pregnancies at implantation, whereas the differences were less pronounced with IVF embryos. Determining the limits of the endometrial plasticity at the onset of implantation should bring new insights on the contribution of the maternal environment to the development of an embryo and the success of pregnancy.bovine ͉ implantation ͉ microarray ͉ nuclear transfer

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Section: Discussionmentioning

confidence: 52%

Endometrium as an early sensor of in vitro embryo manipulation technologies

Mansouri-Attia

Sandra

Aubert

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

199

185

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“…These findings taken together with the observation that VEGF and its receptors are down-regulated in placental samples of pre-eclampsia (Zhou et al 2002, Jarvenpaa et al 2009) suggest that a defect in angiogenic function may result in defective trophoblastic invasion and placentation process (Jauniaux et al 2003, Prefumo et al 2004, Ferretti et al 2007). The suggestion is corroborated by the observation that timed systemic administration of VEGF Mab in the peri-implantation period in the rhesus monkey resulted in compromised expression of VEGF and its receptors along with shallow invasion and pregnancy failure in the rhesus monkey .…”

Section: Anti-vegf On Implantation-stage Endometriummentioning

confidence: 96%

IGF2, IGF binding protein 1, and matrix metalloproteinases 2 and 9 in implantation-stage endometrium following immunoneutralization of vascular endothelial growth factor in the rhesus monkey

Ghosh¹,

Najwa²,

Khan³

et al. 2011

Reproduction

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Blastocyst implantation in the rhesus monkey is inhibited by administration of antibody against vascular endothelial growth factor (VEGF) A during peri-implantation period with no change in the circulatory concentrations of estradiol, progesterone, and VEGF. In this study, we have investigated the effect of administration of a MAB to VEGFA on days 5 and 10 after ovulation upon the mRNA expression, immunopositive protein expression, and immunohistological localization of IGF2, IGF binding protein 1 (IGFBP1) and matrix metalloproteinases (MMPs) 2 and 9 in the implantation-stage endometrium collected on day 13 after ovulation from fecund cycles of rhesus monkeys. The comparison between isotype-matched IgG (control; nZ8)-and VEGF antibody (VEGF Mab; nZ8)-treated animals revealed higher (P!0.05) IGF2 in lacunar and villous syncytiotrophoblasts, trophoblast cell columns, migrating extravillous trophoblast cells, and endovascular trophoblast cells in control animals, but with no change in the various cell types of maternal endometrium between the two groups. No change in IGFBP1 expression in the endometrium was observed between the two groups. MMPs 2 and 9 were detected in syncytiotrophoblast in lacunae and villi, trophoblast cell columns, and extravillous trophoblast cells in control samples. MMP9 transcript expression in maternal endometrium and its immunopositivity in endometrial stroma and trophoblast cells were lower (P!0.05) with no change in MMP2 level in VEGF Mab-exposed samples compared with those in control samples. A functional network involving VEGF, IGF2, and MMP9 in early placental trophoblast cells and maternal endometrium appears to be important for normal placentation.

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“…31 In contrast, in preeclampsia, both HIF-1a and HIF-2a are overexpressed. [32][33][34] There is also evidence to suggest that the impairment of protein degradation rather than increased synthesis causes the inadequate oxygen-dependent reduction of HIF-1a protein in pre-eclamptic placentas. 25 Based on the above data, we assume that the regulation of HIFs in the placentas of FGR-affected pregnancies is mainly achieved through protein stabilisation (post-translational modification), 17 which could explain why we did not observe large-scale variations in the expression levels of HIFs.…”

Section: Discussionmentioning

confidence: 99%

Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction

Gourvas

Sifakis

Dalpa

et al. 2010

BJOG

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Objective To investigate the role of the hypoxia-inducible factor (HIF) pathway in fetal growth restriction (FGR).Design A case-control study.Setting Research laboratory and gynaecology clinic.Sample Twenty placentas from normal pregnancies and 20 from FGR pregnancies.Methods RNA extraction, cDNA synthesis, quantitative real-time polymerase chain reaction (qRT-PCR) assay, statistical analysis.Main outcome measures mRNA expression of HIF-1a, HIF-2a and HIF-b (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF-a subunits.Results No statistically significant differences in the transcription levels of ARNT and HIF-2a were found between FGR and normal placentas. By contrast, PHD3 and HIF-1a mRNA were downregulated in FGR placentas. PHD3 mRNA expression was associated with gestational age at delivery (P = 0.008), birthweight centile (P = 0.029) and abnormal umbilical artery (UA) Doppler measurements (P = 0.034).Conclusions As PHD3 regulates the HIF-mediated hypoxic response in FGR, we deduce that fetal adaptation to hypoxia ranges from impaired to adequate, as observed by the gradient of PHD3 downregulation in relation to the severity of FGR.

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Altered expression of angiogenesis-related placental genes in pre-eclampsia associated with intrauterine growth restriction

Abstract: Our results show new targets for research to understand the mechanisms leading to pre-eclampsia.

Cited by 57 publications

References 25 publications

Endometrium as an early sensor of in vitro embryo manipulation technologies

Endometrium as an early sensor of in vitro embryo manipulation technologies

IGF2, IGF binding protein 1, and matrix metalloproteinases 2 and 9 in implantation-stage endometrium following immunoneutralization of vascular endothelial growth factor in the rhesus monkey

Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction

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